The neural circuitry of the dorsal horn of the spinal cord forms the basis for the mechanisms of pain and neuralgia. Our lab has made significant inroads in understanding the neuronal connectivity which subserves these sensory phenomena through experiments involving multiple markers to identify interactions between neural elements. In situ hybridization histochemistry was used to identify dynorphin neurons in the spinal cord and chart their increased response in a rat model of peripheral inflammation and hyperalgesia. Autoradiographic localization of an oligodeoxyribonucleotide probe complementary to a portion of preprodynorphin mRNA, marked neurons in superficial dorsal horn laminae I and II and deeper laminae V and VI as responding to the peripheral inflammation by increased transcription. These data provide evidence for opioid modulation of nociceptive neural circuits in these two distinct spinal locations. Development changes in primary afferent axons following neonatal administration of capsaicin, a selective neurotoxin, were examined. Initially, the thermal nociceptive threshold was significantly different in the capsaicin-treated animals as compared to controls. However, the threshold decreased between 8 and 16 weeks of age. This change was paralleled by an increase in CGRP immunoreactive axons in the dorsal horn. In contrast, a similar increase in SP immunoreactive axons was not recognized. These data indicate that there is a time dependent return of thermal sensitivity in capsaicin-treated rats between 8 and 16 weeks of age, and that the reduction in thermal nociceptive threshold may be related to alterations in CGRP immunoreactive primary afferent axons.